Vitamin D vs Infections, Part 1 of a series

In this series, from my book The Defeat Of COVID, I discuss the immune system vs SARS-CoV-2, (Part 1), vitamin D’s role in innate immunity (Part 2), adaptive immunity (Parts 3-4) and dosing (Part 5).

Introduction

The time to think about adequate vitamin D levels is before COVID or other respiratory viral infections are an imminent problem.   Is it possible to die from COVID while maintaining adequate serum levels of Vitamin D?  COVID is attributed to infection with SARS-CoV-2 coronavirus.  SARS, or Severe Acute Respiratory Distress Syndrome is a known risk of vitamin D deficiency, and has been reversed and eliminated by supplementation of the same, as I will show throughout this series.  Population studies and studies of hospitalized patients with COVID-19 diagnosis show strongly improved outcomes with higher serum levels of vitamin D.  Unlike vaccination, which acts on a small portion of immune function, vitamin D receptors are ubiquitous throughout the entire immune system.  There is no cell line where vitamin D receptors have been determined to be absent.   Vitamin D activates all known immune system functions, and thwarts viral pathogenesis at each step that has been studied.  But vitamin D is also essential in stopping some of the most severe over-reactions of the immune system to viral invasion, such as cytokine storm.  Is COVID a manifestation of severe deficiency of vitamin D?

Is there a species that has ever existed that was without macroscopic and microscopic predators?  In the animal kingdom, we can use our five senses and our wits to detect, evade and escape or chase away our macroscopic predators.  The task is more challenging with microscopic predators, typically thought of as pathogenic microbes.  Because our senses are not very useful in awareness of either microbial presence nor of our vulnerability to the same, there are different defenses employed by animals, plants and even microbes against pathogenic microbes.

In this series, I examine the chain of events that occurs when the number of virions in the body rises, specifically the human immune response to SARS-CoV-2, the infectious agent in COVID, considering both the role of this respiratory virus and the body’s response to it, as well as the particular role of vitamin D in this process.  

It has been found, in clinical studies throughout the world, that Vitamin D has a role in every known aspect of human immune function.  Discussion of human immune response to this or any other pathogen, without a consideration of the ubiquitous role of Vitamin D, is therefore necessarily incomplete.  To give an example of a different intervention, vaccines stimulate antibodies, which are an aspect of the adaptive immune response to pathogenic assault.  Vaccines therefore are active in a portion of total immune function, but Vitamin D is active in all human immune functions, as will be shown in this series.

The Innate Immune System vs COVID-19

Innate immunity is common throughout the animal kingdom, and 99% of the animal kingdom relies only on the innate system, not having an equivalent to the human adaptive immune system.  Epithelial barriers, both skin and mucosa, are the first line of defense.  As such, the most expendable skin, the metabolically inactive keratinocytes, are a shield against pathogens, so long as the epidermis is not pierced.  When the skin is lacerated, abraded or otherwise compromised, innate immunity is the organism’s first response.  Gathering of leukocytes and plasma-borne proteins comprise the early inflammatory process.  In the case of cells that have been infected by viruses, those cells are killed by natural killer cells.  Type I interferons stop viral replication in infected cells.  The amnesic role of the innate immune system is that all pathogens of the same type are treated identically whether similar pathogens have invaded previously or not.  It is only later that the adaptive immune system, particularly memory cells, will respond in a more precisely targeted way.

COVID is observed to have an incubation period of 5 days, and if hospitalization occurs, it generally happens within the following 7 days. [1]  80% of the patients who develop symptoms generally get better on their own.  The human immune system has been key to this success of the majority.  The innate immune system is almost exclusively relied on through early childhood, and gradually weakens with age, while the importance and capability of, and reliance on, the adaptive immune system increases with age to the point of near exclusive reliance on adaptive immunity in the elderly.    It has been observed that innate immune response has been key to successful outcome against COVID [2] which may account for the strong age differential of this disease, of which the average age of death is 81, and children are unaffected.[3] 

Fever is one of the early symptoms of COVID, if the body is capable of mounting a robust fever.  It has been found that fever of 39 degrees Celsius stimulates production in the lymphocytes of more than 10-fold interferon gamma than cells in the same individuals at normal basal temperature.[4]  The importance of interferons in the body’s fight against viruses can hardly be overstated.

The innate system is the first-responding activity of the immune system.   In the innate immune system interferons are the best understood and likely most devastating cytokine produced against viruses.  All of our cells have Type I interferons, knows as interferon alpha and interferon beta, which are the first to be activated in the event of a new infection.

SARS-CoV-2 virus has been found to interfere with the body’s production of interferon.  This is a mechanism of how the virus advances through the immune system.    But later when the virus has actively replicated, it has been found that “active viral replication later results in hyper-production of type I interferon and influx of neutrophils and macrophages, which are the major source of inflammatory cytokines.”  The authors concluded that a pathogenic mechanism of SARS-CoV-2 is that it “probably induces delayed Type I interferons and loss of viral control in an early phase of infection.”[5]  Or that is, the patients who were found to succumb to the most severe disease outcomes were those that could not produce an early immune response against the virus, particularly those with low Type I interferon activity, as measured by Type I interferon activity and presence in the blood.[6]  Patients with auto-antibodies against Type I interferons all had low or undetectable interferons and had severe or life-threatening COVID-19, and none of them had mild cases.[7]

Because of the 10-fold increase in interferon production at a body temperature of 39 degrees Celsius as discussed above, it may be useful to think of strategies to enhance this mechanism.  Anti-pyretic medications may be avoided during this time.  The naturopathic medical curriculum has for over a century incorporated constitutional hydrotherapy along with the contemporary medical curriculum as well as other traditionally naturopathic fields, such as botanical medicine and nutrition.  Practitioners have used successive applications of hot and cold, and or sauna or infrared strategies to induce higher temperature in their patients under controlled conditions to avoid burns. [8]

Coronavirus, electron micrograph

This will be a weekly series exploring various aspects of vitamin D and its role in immune function and against SARS-CoV-2 infection.

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[1] C Huang, Y Wang, et al.  Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.  Lancet.  Feb 15 2020.  395 (10223): 497-506. https://pubmed.ncbi.nlm.nih.gov/31986264/

[2] E Prompetchara, C Ketloy, et al.  Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic.  Asian Pac J Allergy Immunol.  Mar 2020.  38 (1). 1-9.  https://pubmed.ncbi.nlm.nih.gov/32105090/

[3] BBC News.  Covid death figures: 10 things we’ve learned.  Oct 6 2020.  https://pubmed.ncbi.nlm.nih.gov/25903964/

[4] J Downing, H Martinez-Valdez, et al.  Hyperthermia in humans enhances interferon-gamma synthesis and alters the peripheral lymphocyte population.  J Interferon Res.  Apr 1988.  8 (2).  143-150.  https://pubmed.ncbi.nlm.nih.gov/3132509/

[5] E Prompetchara, C Ketloy, et al.  Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic.  Asian Pac J Allergy Immunol.  Mar 2020.  38 (1). 1-9.  https://pubmed.ncbi.nlm.nih.gov/32105090/

[6] J Hadjadj, N Yatim, et al.  Impaired Type I interferon activity and inflammatory responses in severe COVID-19 patients.  Science.  Aug 7 2020.  369 (6504).  718-724.  https://pubmed.ncbi.nlm.nih.gov/32661059/

[7] P Bastard, L Rosen, et al.  Autoantibodies against type I IFNs in patients with life threatening COVID-19.  Science.  Oct 23 2020.  370 (6515). eabd4585.   https://pubmed.ncbi.nlm.nih.gov/32972996/

[8] E Ernst, E Pecho, et al.  Regular sauna bathing and the incidence of common colds.  Ann Med.  1990. 22 (4). 225-227.  https://pubmed.ncbi.nlm.nih.gov/2248758/